PRKD1 [The Human Chemical-Genetic Interaction Map Project]

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======= PRKD1 =======


== Gene Information ==
  * **<color #00a2e8>Official Symbol</color>**: PRKD1
  * **<color #00a2e8>Official Name</color>**: protein kinase D1
  * **<color #00a2e8>Aliases and Previous Symbols</color>**: N/A
  * **<color #00a2e8>Entrez ID</color>**: [[https://www.ncbi.nlm.nih.gov/gene/?term=5587|5587]]
  * **<color #00a2e8>UniProt</color>**: [[https://www.uniprot.org/uniprot/Q15139|Q15139]]
  * **<color #00a2e8>Interactions</color>**: [[https://thebiogrid.org/search.php?search=PRKD1&organism=9606|BioGRID]]
  * **<color #00a2e8>PubMed articles</color>**: [[https://www.ncbi.nlm.nih.gov/pubmed/?term=gene%20PRKD1|Open PubMed]]
  * **<color #00a2e8>OMIM</color>**: [[https://omim.org/entry/605435|Open OMIM]]

== Function Summary ==
  * **<color #00a2e8>Entrez Summary</color>**:  The protein encoded by this gene is a serine/threonine protein kinase involved in many cellular processes, including Golgi body membrane integrity and transport, cell migration and differentiation, MAPK8/JNK1 and Ras pathway signaling, MAPK1/3 (ERK1/2) pathway signaling, cell survival, and regulation of cell shape and adhesion. [provided by RefSeq, Jan 2017]. 
  * **<color #00a2e8>UniProt Summary</color>**:  Serine/threonine-protein kinase that converts transient diacylglycerol (DAG) signals into prolonged physiological effects downstream of PKC, and is involved in the regulation of MAPK8/JNK1 and Ras signaling, Golgi membrane integrity and trafficking, cell survival through NF-kappa-B activation, cell migration, cell differentiation by mediating HDAC7 nuclear export, cell proliferation via MAPK1/3 (ERK1/2) signaling, and plays a role in cardiac hypertrophy, VEGFA-induced angiogenesis, genotoxic-induced apoptosis and flagellin-stimulated inflammatory response. Phosphorylates the epidermal growth factor receptor (EGFR) on dual threonine residues, which leads to the suppression of epidermal growth factor (EGF)-induced MAPK8/JNK1 activation and subsequent JUN phosphorylation. Phosphorylates RIN1, inducing RIN1 binding to 14-3-3 proteins YWHAB, YWHAE and YWHAZ and increased competition with RAF1 for binding to GTP-bound form of Ras proteins (NRAS, HRAS and KRAS). Acts downstream of the heterotrimeric G-protein beta/gamma-subunit complex to maintain the structural integrity of the Golgi membranes, and is required for protein transport along the secretory pathway. In the trans-Golgi network (TGN), regulates the fission of transport vesicles that are on their way to the plasma membrane. May act by activating the lipid kinase phosphatidylinositol 4-kinase beta (PI4KB) at the TGN for the local synthesis of phosphorylated inositol lipids, which induces a sequential production of DAG, phosphatidic acid (PA) and lyso-PA (LPA) that are necessary for membrane fission and generation of specific transport carriers to the cell surface. Under oxidative stress, is phosphorylated at Tyr-463 via SRC-ABL1 and contributes to cell survival by activating IKK complex and subsequent nuclear translocation and activation of NFKB1. Involved in cell migration by regulating integrin alpha-5/beta-3 recycling and promoting its recruitment in newly forming focal adhesion. In osteoblast differentiation, mediates the bone morphogenetic protein 2 (BMP2)- induced nuclear export of HDAC7, which results in the inhibition of HDAC7 transcriptional repression of RUNX2. In neurons, plays an important role in neuronal polarity by regulating the biogenesis of TGN-derived dendritic vesicles, and is involved in the maintenance of dendritic arborization and Golgi structure in hippocampal cells. May potentiate mitogenesis induced by the neuropeptide bombesin or vasopressin by mediating an increase in the duration of MAPK1/3 (ERK1/2) signaling, which leads to accumulation of immediate-early gene products including FOS that stimulate cell cycle progression. Plays an important role in the proliferative response induced by low calcium in keratinocytes, through sustained activation of MAPK1/3 (ERK1/2) pathway. Downstream of novel PKC signaling, plays a role in cardiac hypertrophy by phosphorylating HDAC5, which in turn triggers XPO1/CRM1-dependent nuclear export of HDAC5, MEF2A transcriptional activation and induction of downstream target genes that promote myocyte hypertrophy and pathological cardiac remodeling. Mediates cardiac troponin I (TNNI3) phosphorylation at the PKA sites, which results in reduced myofilament calcium sensitivity, and accelerated crossbridge cycling kinetics. The PRKD1-HDAC5 pathway is also involved in angiogenesis by mediating VEGFA-induced specific subset of gene expression, cell migration, and tube formation. In response to VEGFA, is necessary and required for HDAC7 phosphorylation which induces HDAC7 nuclear export and endothelial cell proliferation and migration. During apoptosis induced by cytarabine and other genotoxic agents, PRKD1 is cleaved by caspase-3 at Asp-378, resulting in activation of its kinase function and increased sensitivity of cells to the cytotoxic effects of genotoxic agents. In epithelial cells, is required for transducing flagellin-stimulated inflammatory responses by binding and phosphorylating TLR5, which contributes to MAPK14/p38 activation and production of inflammatory cytokines. May play a role in inflammatory response by mediating activation of NF-kappa- B. May be involved in pain transmission by directly modulating TRPV1 receptor. Plays a role in activated KRAS-mediated stabilization of ZNF304 in colorectal cancer (CRC) cells (PubMed:24623306). Regulates nuclear translocation of transcription factor TFEB in macrophages upon live S.enterica infection (By similarity). {ECO:0000250|UniProtKB:Q62101, ECO:0000269|PubMed:10523301, ECO:0000269|PubMed:10764790, ECO:0000269|PubMed:12505989, ECO:0000269|PubMed:12637538, ECO:0000269|PubMed:15471852, ECO:0000269|PubMed:17442957, ECO:0000269|PubMed:18332134, ECO:0000269|PubMed:18509061, ECO:0000269|PubMed:19135240, ECO:0000269|PubMed:19211839, ECO:0000269|PubMed:24623306}.

<button type='primary' size='sm' modal='Pfam_Domains'>Pfam Domains</button>
<button type='primary' size='sm' modal='GO_terms'>GO Terms</button>


<modal id='Pfam_Domains' size='lg' title='Pfam Domains'>
|PH|
|C1 1|
|Pkinase Tyr|
|Pkinase|
</modal>

<modal id='GO_terms' size='lg' title='GO Terms'>
|protein kinase D signaling|
|positive regulation of endothelial cell chemotaxis by VEGF-activated vascular endothelial growth factor receptor signaling pathway|
|positive regulation of histone deacetylase activity|
|positive regulation of cell migration by vascular endothelial growth factor signaling pathway|
|cellular response to hydroperoxide|
|positive regulation of deacetylase activity|
|regulation of histone deacetylase activity|
|regulation of deacetylase activity|
|regulation of integrin-mediated signaling pathway|
|protein kinase C activity|
|positive regulation of endothelial cell chemotaxis|
|positive regulation of histone deacetylation|
|vascular endothelial growth factor signaling pathway|
|positive regulation of CREB transcription factor activity|
|response to hydroperoxide|
|regulation of endothelial cell chemotaxis|
|positive regulation of protein deacetylation|
|regulation of histone deacetylation|
|positive regulation of phosphatidylinositol 3-kinase activity|
|autophagosome membrane|
|regulation of keratinocyte proliferation|
|positive regulation of lipid kinase activity|
|cellular response to vascular endothelial growth factor stimulus|
|regulation of protein deacetylation|
|cellular response to amino acid starvation|
|negative regulation of endocytosis|
|response to amino acid starvation|
|positive regulation of phospholipid metabolic process|
|regulation of phosphatidylinositol 3-kinase activity|
|positive regulation of blood vessel endothelial cell migration|
|positive regulation of osteoblast differentiation|
|regulation of lipid kinase activity|
|vascular endothelial growth factor receptor signaling pathway|
|kinase activity|
|peptidyl-threonine phosphorylation|
|positive regulation of ossification|
|regulation of phospholipid metabolic process|
|regulation of blood vessel endothelial cell migration|
|positive regulation of histone modification|
|peptidyl-threonine modification|
|sphingolipid biosynthetic process|
|integrin-mediated signaling pathway|
|positive regulation of endothelial cell proliferation|
|positive regulation of endothelial cell migration|
|positive regulation of chromatin organization|
|positive regulation of peptidyl-serine phosphorylation|
|regulation of osteoblast differentiation|
|positive regulation of autophagy|
|regulation of endothelial cell proliferation|
|membrane lipid biosynthetic process|
|Golgi organization|
|positive regulation of chemotaxis|
|regulation of peptidyl-serine phosphorylation|
|positive regulation of epithelial cell migration|
|positive regulation of lipid metabolic process|
|regulation of histone modification|
|cellular response to starvation|
|positive regulation of NF-kappaB transcription factor activity|
|sphingolipid metabolic process|
|regulation of endothelial cell migration|
|positive regulation of angiogenesis|
|trans-Golgi network|
|positive regulation of chromosome organization|
|peptidyl-serine phosphorylation|
|positive regulation of vasculature development|
|positive regulation of I-kappaB kinase/NF-kappaB signaling|
|positive regulation of epithelial cell proliferation|
|regulation of chromatin organization|
|regulation of ossification|
|protein autophosphorylation|
|response to starvation|
|peptidyl-serine modification|
|membrane lipid metabolic process|
|regulation of endocytosis|
|regulation of chemotaxis|
|regulation of epithelial cell migration|
|cellular response to nutrient levels|
|regulation of I-kappaB kinase/NF-kappaB signaling|
|cellular response to oxidative stress|
|Ras protein signal transduction|
|positive regulation of DNA-binding transcription factor activity|
|cellular response to extracellular stimulus|
|positive regulation of neuron projection development|
|regulation of protein stability|
|regulation of angiogenesis|
|angiogenesis|
|small GTPase mediated signal transduction|
|regulation of vasculature development|
|regulation of autophagy|
|regulation of epithelial cell proliferation|
|cellular response to external stimulus|
|regulation of chromosome organization|
|protein serine/threonine kinase activity|
|positive regulation of cellular catabolic process|
|positive regulation of neuron differentiation|
|Golgi vesicle transport|
|positive regulation of cell projection organization|
|response to oxidative stress|
|regulation of lipid metabolic process|
|blood vessel morphogenesis|
|endomembrane system organization|
|regulation of DNA-binding transcription factor activity|
|positive regulation of catabolic process|
|positive regulation of neurogenesis|
|negative regulation of transport|
|blood vessel development|
|regulation of neuron projection development|
|inflammatory response|
|response to nutrient levels|
|positive regulation of cell migration|
|cellular response to growth factor stimulus|
|vasculature development|
|transmembrane receptor protein tyrosine kinase signaling pathway|
|cardiovascular system development|
|positive regulation of cell motility|
|response to growth factor|
|response to extracellular stimulus|
|positive regulation of nervous system development|
|positive regulation of cellular component movement|
|positive regulation of cell development|
|regulation of vesicle-mediated transport|
|positive regulation of locomotion|
|positive regulation of kinase activity|
|lipid biosynthetic process|
|positive regulation of response to external stimulus|
|positive regulation of organelle organization|
|tube morphogenesis|
|positive regulation of transferase activity|
|regulation of neuron differentiation|
|regulation of plasma membrane bounded cell projection organization|
|negative regulation of cellular component organization|
|regulation of cell projection organization|
|enzyme linked receptor protein signaling pathway|
|innate immune response|
|positive regulation of hydrolase activity|
|regulation of neurogenesis|
|regulation of cellular catabolic process|
|tube development|
|regulation of cell migration|
|circulatory system development|
|regulation of kinase activity|
|peptidyl-amino acid modification|
|anatomical structure formation involved in morphogenesis|
|regulation of cell motility|
|positive regulation of cell population proliferation|
|apoptotic process|
|regulation of nervous system development|
|regulation of cell development|
|defense response to other organism|
|cellular lipid metabolic process|
|positive regulation of cell differentiation|
|protein phosphorylation|
|regulation of transferase activity|
|regulation of locomotion|
|Golgi apparatus|
|regulation of cellular component movement|
|regulation of catabolic process|
|negative regulation of cell death|
|positive regulation of protein phosphorylation|
|positive regulation of intracellular signal transduction|
|programmed cell death|
|cellular response to oxygen-containing compound|
|positive regulation of phosphorylation|
|regulation of anatomical structure morphogenesis|
|identical protein binding|
|cell death|
|regulation of response to external stimulus|
|positive regulation of phosphate metabolic process|
|positive regulation of phosphorus metabolic process|
|positive regulation of cellular component organization|
|lipid metabolic process|
|positive regulation of transcription by RNA polymerase II|
|positive regulation of protein modification process|
|regulation of hydrolase activity|
|phosphorylation|
|regulation of organelle organization|
|response to other organism|
|response to external biotic stimulus|
|response to biotic stimulus|
|defense response|
|positive regulation of developmental process|
|organonitrogen compound biosynthetic process|
|positive regulation of catalytic activity|
|regulation of protein phosphorylation|
|ATP binding|
|generation of neurons|
|positive regulation of transcription, DNA-templated|
|response to oxygen-containing compound|
|regulation of phosphorylation|
|positive regulation of cellular protein metabolic process|
|regulation of cell population proliferation|
|neurogenesis|
|positive regulation of nucleic acid-templated transcription|
|positive regulation of RNA biosynthetic process|
|positive regulation of signal transduction|
|regulation of cell death|
|intracellular signal transduction|
|cellular response to stress|
|positive regulation of protein metabolic process|
|positive regulation of RNA metabolic process|
|positive regulation of multicellular organismal process|
|positive regulation of molecular function|
|regulation of phosphate metabolic process|
|regulation of phosphorus metabolic process|
|regulation of cell differentiation|
|positive regulation of cell communication|
|positive regulation of signaling|
|regulation of intracellular signal transduction|
|regulation of protein modification process|
|regulation of transport|
|immune response|
|positive regulation of nucleobase-containing compound metabolic process|
|positive regulation of macromolecule biosynthetic process|
|vesicle-mediated transport|
|positive regulation of cellular biosynthetic process|
|positive regulation of gene expression|
|positive regulation of biosynthetic process|
</modal>
\\

 === CRISPR Data ===
<button type='default' size='small' modal='Compound_Hit'>Compound Hit</button>
<button type='primary' size='small' modal='Most_Correlated_Genes'>Most Correlated Genes in Chemogenomics</button>
<button type='primary' size='small' modal='Essential_Avana'>Tissues where Essential in the Avana Dataset (DepMap 20Q1)</button>

<modal id='Compound_Hit' size='lg' title='Compound Hit'>
No hits were found.
</modal>

<modal id='Most_Correlated_Genes' size='lg' title='Most Correlated Genes in Chemogenomics'>
^Gene^Correlation^
|[[:human genes:r:rrm1|RRM1]]|0.476|
</modal>

<modal id='Essential_Avana' size='lg' title='Tissues where Essential in the Avana Dataset (DepMap 20Q1)'>
Global Fraction of Cell Lines Where Essential: 0/726
^Tissue^Fraction Of Cell Lines Where Essential^
|1290807.0|0/1|
|909776.0|0/1|
|bile duct|0/28|
|blood|0/28|
|bone|0/25|
|breast|0/33|
|central nervous system|0/56|
|cervix|0/4|
|colorectal|0/17|
|esophagus|0/13|
|fibroblast|0/1|
|gastric|0/15|
|kidney|0/21|
|liver|0/20|
|lung|0/75|
|lymphocyte|0/14|
|ovary|0/26|
|pancreas|0/24|
|peripheral nervous system|0/16|
|plasma cell|0/15|
|prostate|0/1|
|skin|0/24|
|soft tissue|0/7|
|thyroid|0/2|
|upper aerodigestive|0/22|
|urinary tract|0/29|
|uterus|0/5|
</modal>

== Essentiality in NALM6  ==
    * **<color #00a2e8>Essentiality Rank</color>**: 3423
    * **<color #00a2e8>Expression level (log2 read counts)</color>**: -0.26 
<button type='primary' size='small' modal='Dist_expr'>Expression Distribution</button>
<modal id='Dist_expr' size='lg' title='PRKD1 Expression in NALM6 Cells: -0.26'>
{{:chemogenomics:nalm6 dist.png?nolink |}}
</modal>